The Effect of Probenecid on Urate Transport in the Rat Kidney

Abstract

p-(Dipropylsulfamyl)benzoic acid (probenecid) has been utilized in clinical practice and in experimental studies to decrease the tubular reabsorption of uric acid ( 1 ). Probenecid is also known to inhibit the secretion of organic acids in the kidney ( 2 ). Despite the extensive use of this agent, its separate effects on the urate reabsorptive and secretory processes have not been examined by direct techniques. The current investigations, therefore, were designed to examine the effects of probenecid on net urate transport, urate reabsorption, and urate secretion using clearance, microinjection, and precession techniques in the rat.

Methods. Male Sprague-Dawley rats anesthetized with Inactin (Promonta, Hamburg, Germany), 100 mg/kg body wt intra-peritoneally, were used for all studies. Probenecid was dissolved in a solution of dilute NaOH to a final concentration of 10-20 mg/ml and was administered in a dose of 100 mg/kg body wt/hr intravenously. In control animals and in control periods of the clearance experiments, diluent alone was infused.

Clearance studies. After a tracheotomy, cannulae were placed in two jugular veins, in a femoral artery, and in the urinary bladder. Body temperature was maintained at 37°. Five percent mannitol in isotonic saline was infused at a rate of 12 ml/hr to match the protocol of the microinjection studies. Through the other venous line, normal saline containing [methoxy-³H]inulin (25 μCi/ ml) was infused at a rate of 1.2 ml/hr. After 60-90 min of equilibration, two control urine samples, 20 min each, were collected. One milliliter of blood was obtained from the femoral artery at the midpoint of each period and was replaced with the same volume of blood from a donor rat. Following collection of control samples, probenecid (100 mg/kg body wt/hr) was infused.